1. Field of the Invention
The present invention relates generally to medical devices and methods. More particularly, the present invention relates to devices and methods for the intraluminal characterization of lesions in blood vessels and other body lumens.
Coronary artery disease resulting from the build-up of atherosclerotic plaque in the coronary arteries is a leading cause of death in the United States and worldwide. The plaque build-up causes a narrowing of the artery, commonly referred to as a lesion, which reduces blood flow to the myocardium (heart muscle tissue). Myocardial infarction (better known as a heart attack) can occur when an arterial lesion abruptly closes the vessel, causing complete cessation of blood flow to portions of the myocardium. Even if abrupt closure does not occur, blood flow may decrease resulting in chronically insufficient blood flow which can cause significant tissue damage over time.
A variety of interventions have been proposed to treat coronary artery disease. For disseminated disease, the most effective treatment is usually coronary artery bypass grafting where problematic lesions in the coronary arteries are bypassed using external grafts. In cases of less severe disease, pharmaceutical treatment is often sufficient. Finally, focused disease can often be treated intravascularly using a variety of catheter-based approaches, such as balloon angioplasty, atherectomy, radiation treatment, stenting, and often combinations of these approaches.
With the variety of treatment techniques which are available, the cardiologist is faced with a challenge of selecting the particular treatment which is best suited for an individual patient. While numerous of diagnostic aids have been developed, no one technique provides all the information which is needed to select a treatment. Angiography is very effective in locating lesions in the coronary vasculature, but provides little information concerning the nature of the lesion. To provide better characterization of the lesion(s), a variety of imaging techniques have been developed for providing a more detailed view of the lesion, including intravascular ultrasound (IVUS), angioscopy, laser spectroscopy, computed tomography (CT), magnetic resonance imaging (MRI), and the like. None of these techniques, however, is completely successful in determining the exact nature of the lesion. In particular, such techniques provide little information regarding whether the plaque is stable or unstable.
Plaques which form in the coronaries and other vessels comprise inflammatory cells, smooth muscles cells, cholesterol, and fatty substances, and these materials are usually trapped between the endothelium of the vessel and the underlying smooth muscle cells. Depending on various factors, including thickness, composition, and size of the deposited materials, the plaques can be characterized as stable or unstable. The plaque is normally covered by a cap and/or an endothelial layer. When the cap and/or endothelial layer is disrupted, the ruptured plaque releases highly thrombogenic constituent materials which are capable of activating the clotting cascade and inducing rapid and substantial coronary thrombosis. Such plaque is referred to as unstable or xe2x80x9cvulnerable,xe2x80x9d and the resulting thrombus formation can cause unstable angina chest pain, acute myocardial infarction (heart attack), sudden coronary death, and stroke. It has recently been proposed that plaque instability, rather than the degree of plaque build-up, should be the primary determining factor for treatment selection.
A variety of approaches for distinguishing stable and unstable plaque in patients have been proposed. Some of the proposals involve detecting a slightly elevated temperature within unstable plaque resulting from inflammation. Other techniques involve exposure of the plaque to infrared light. It has also been proposed to introduce radiolabeled materials which have been shown by autoradiography to bind to stable and unstable plaque in different ways. External detection of the radiolabels, however, greatly limits the sensitivity of these techniques and makes it difficult to determine the precise locations of the affected regions. Thus far, none of these technologies has possessed sufficient sensitivity or resolution necessary to reliably characterize the plaque at the cellular level in the intact animal or man.
For all of these reasons, it would be desirable to provide improved methods and apparatus for distinguishing between stable and unstable plaque within the coronary and other patient vasculature. It would be further desirable if such methods and techniques could be applied to characterizing lesions in other body lumens, which are associated with other disease conditions. The methods and devices of the present invention should preferably be able to be implemented in situ, i.e., within the body lumen being assessed, and should preferably be able to interrogate the body lumen over a relatively long distance to characterize disseminated disease in an efficient fashion. The methods and devices should provide highly sensitive detection so that even minor differences between regions of plaque or other lesions can be determined, and should permit assessment in real time, preferably without the need for prolonged placement of the devices within a patient. At least some of these objectives will be met by the inventions described hereinafter.
2. Description of the Background Art
The use of radiolabeled agents for detecting atherosclerotic lesions is described in the medical literature. See, for example, Elmaleh et al. (1998) Proc. Natl. Acad. Sci. USA 95:691-695; Vallabhajosula and Fuster (1997) J Nucl. Med. 38:1788-1796); Demos et al. (1997) J Pharm. Sci. 86:167-171; Narula et al. (1995) Circulation 92: 474-484; and Lees et al. (1998) Arteriosclerosis 8:461-470. U.S. Pat. No. 4,660,563, describes the injection of radiolabeled lipoproteins into a patient where the lipoproteins are taken up into regions of arteriosclerotic lesions to permit early detection of those lesions using an external scintillation counter. U.S. Pat. No. 5,811,814, describes and intravascular radiation-detecting catheter. The catheter is used to locate tagged red blood cells that may accumulate, for example, in an aneurysm. U.S. Pat. No. 5,429,133, describes a laparoscopic probe for detecting radiation concentrated in solid tissue tumors. Miniature and flexible radiation detectors intended for medical use are produced by Intra-Medical LLC, Santa Monica, Calif. (www.intra-medical.com). See also U.S. Pat. Nos. 4,647,445; 4,877,599; 4,937,067; 5,510,466; 5,711,931; 5,726,153; and WO 89/10760.
Methods, systems, and kits, are provided for assessing characteristics of lesions and other target sites within body lumens, particularly atherosclerotic lesions within a patient""s vasculature, including the coronary vasculature, peripheral vasculature, and cerebral vasculature. The present invention relies on introducing a labeled marker, typically a radiolabeled marker, to the patient in such a way that the marker localizes within the lesion or target site in some manner which enables or facilitates assessment of that target site. Introduction of the labeled marker can be systemic, e.g., by injection or infusion to the patient""s blood circulation for evaluation of lesions in the vasculature or other body lumens. Alternatively, introduction of the labeled markers can be local, e.g., by catheter delivery directly to a target site within a blood vessel or other body lumen. Moreover, the labeled marker could be introduced systemically and locally in various combinations. After introduction to the patient, the labeled marker is taken up by the lesion or other target site, and the amount of marker (accumulation), rate of uptake, distribution of marker, or other marker characteristics then determined in order to facilitate or enable diagnosis or other evaluation of the lesion. In particular, according to the present invention, the amount, rate of uptake, and/or distribution of the marker at or near the lesion or other target site is measured in situ using a detector which has been introduced into the body lumen and positioned in a known or measurable relationship to the lesion or other target site.